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迈伦·戈登奖论文:微生物、T 细胞多样性与肤色。

Myron Gordon Award paper: Microbes, T-cell diversity and pigmentation.

机构信息

Department of Dermatology, Microbiology and Immunology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University at Chicago, Chicago, IL, USA.

出版信息

Pigment Cell Melanoma Res. 2021 Mar;34(2):244-255. doi: 10.1111/pcmr.12957. Epub 2021 Jan 27.

Abstract

Melanocytes are static, minimally proliferative cells. This leaves them vulnerable in vitiligo. Yet upon malignant transformation, they form vicious tumors. This profound switch in physiology is accompanied by genetic change and is driven by environmental factors. If UV exposure in younger years supports malignant transformation and melanoma formation, it can likewise impart mutations on melanocytes that reduce their viability, to initiate vitiligo. A wide variety of microbes can influence these diametrically opposed outcomes before either disease takes hold. These microbes are vehicles of change that we are only beginning to study. Once a genetic modification occurs, there is a wide variety of immune cells ready to respond. Though it does not act alone, the T cell is among the most decisive responders in this process. The same biochemical process that offered the skin protection by producing melanin can become an Achilles heel for the cell when the T cells target melanosomal enzymes or, on occasion, neoantigens. T cells are precise, determined, and consequential when they strike. Here, we probe the relationship between the microbiome and its metabolites, epithelial integrity, and the activation of T cells that target benign and malignant melanocytes in vitiligo and melanoma.

摘要

黑素细胞是静止的、增殖能力有限的细胞。这使它们在白癜风中容易受到伤害。然而,一旦发生恶性转化,它们就会形成恶性肿瘤。这种生理学上的深刻转变伴随着遗传变化,并受环境因素的驱动。如果年轻时的紫外线暴露支持恶性转化和黑色素瘤的形成,它同样会导致黑素细胞的突变,从而引发白癜风。在任何一种疾病发生之前,各种各样的微生物都可以影响这两种截然相反的结果。这些微生物是我们才刚刚开始研究的变化载体。一旦发生基因改变,就会有各种各样的免疫细胞准备好做出反应。尽管 T 细胞不是唯一的作用因素,但在这个过程中,它是最具决定性的反应者之一。当 T 细胞针对黑色素体酶或偶尔的新抗原时,产生黑色素以保护皮肤的生化过程会成为细胞的致命弱点。T 细胞在攻击时非常精确、果断且有影响力。在这里,我们探讨了微生物组及其代谢物、上皮完整性以及针对白癜风和黑色素瘤中良性和恶性黑素细胞的 T 细胞激活之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f62/9285650/b071a7bfec5c/nihms-1814525-f0001.jpg

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